Current and emerging diagnostic and management approaches for idiopathic intracranial hypertension

ABSTRACT

Introduction

Idiopathic intracranial hypertension is characterized by raised intracranial pressure that triggers disabling headaches and can cause permanent visual loss. There is an increased incidence and prevalence of the condition linked to location-specific obesity rates. There are no licensed treatments for the condition. The majority of approaches to managing the disease prioritize resolution of papilledema. However, evidence is emerging that idiopathic intracranial hypertension is a systemic metabolic disease.

Areas covered

The aim of this review is to present the emerging pathophysiology evidence which is leading to novel targeted therapeutics. The diagnostic pathway is outlined. The current and potential management approaches for idiopathic intracranial hypertension are also discussed.

Expert opinion

Idiopathic intracranial hypertension is a condition with metabolic dysregulation with systemic manifestations that are present over and above what can be expl.ained by obesity alone. While most of the current management of this condition focuses on the eyes, future management needs to address the disabling headaches and the systemic risks of preeclampsia, gestational diabetes, and major cardiovascular events.

KEYWORDS:

• Bariatric surgery
• glucagon like peptide 1
• headache
• intracranial pressure
• optical coherence tomography
• papilledema
• pregnancy
• prognosis

Article highlights

• IIH is emerging as a systemic metabolic disease. Many of the newly recognized disease features are in excess than that driven by the presence of obesity. These include an increased twofold risk of cardiovascular disease, reduced fertility and the pregnancy complications of pre-eclampsia and gestational diabetes.

• Adipose tissue in IIH has a unique profile of transcription and metabolic dysregulation driving lipogenesis and promoting increased adipose deposition. There is evidence of increased truncal adiposity, insulin resistance, and hyperleptinemia.

• The systemic hormonal signature is characterized by hyperandrogenic and systemic glucocorticoid dysregulation.

• GLP-1 R is expressed in the human choroid plexus. A GLP-1 R agonist has been shown to be safe and reduces ICP acutely and up to 12 weeks in a phase 2 RCT.

• Bariatric surgery has recently been shown to be superior to a dietary intervention at sustained disease remission out to two years.

• Headache remains the most common symptom and an unmet clinical challenge, with open label evidence showing the successful use of calcitonin gene-related peptide monoclonal antibody therapy. This points toward new mechanistic insights to sensitization of the trigeminovascular pathways in IIH headache.

Declaration of interest

SP Mollan reports consultancy fees from Invex therapeutics (Trial Steering Group and Independent Adjudication Committee Fees 2022) and the Velux foundation (2021). SP Mollan also reports serving on the advisory Boards of Invex Therapeutics (2020/2021/2022) and Gensight (2022) and has received speaker fees from Heidelberg Engineering (2020/2021/2022), Chugai (2021/2022) and Chiesi Farmaceutici (2020/2021). SP Mollan also reports royalties/licenses from/with Springer publishing and is a member of the following organizational arms, without re-imbursement: the North American Neuro-Ophthalmology Society (Abstract committee, Membership committee, International Relations Committee), United Kingdom Neuro-Ophthalmology Society (Secretary), British Isles Neuro-Ophthalmology Club (Treasurer) and United Kingdom Cerebrospinal Fluid Annual Meeting (Convener). AJ Sinclair reports personal fees, share option and shareholding with Invex therapeutics as well as speaker fees from Allergan-AbbVie, Novartis, and Teva UK. She also receives grants from Amgen Inc, Chiesi and Lundbeck as well as research grants/funding from the National Institute for Health Research and the Medical Research Council. Finally, AJ Sinclair also receives royalties or holds licenses with/from Springer publishing.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

References

Papers of special note have been highlighted as either of interest (•) or of considerable interest (••) to readers.

Additional information

Funding

AJ Sinclair is funded by a Sir Jules Thorn award for Biomedical Science.